A Dose-Optimization Study of Aldurazyme® (Laronidase) in Patients With Mucopolysaccharidosis I (MPS I) Disease

Condition(s) targeted: Mucopolysaccharidosis I; Hurler's Syndrome; Hurler-Scheie Syndrome; Scheie Syndrome

Intervention: Aldurazyme (Recombinant Human Alpha-L-Iduronidase) (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Genzyme

The main purpose of this study is to evaluate differences in the pharmacodynamic response of 4 Aldurazyme® (laronidase) dose regimens in patients with Mucopolysaccharidosis I (MPS I) disease through measuring urinary GAG levels, liver volume, and functional tests (6-minute walk test).

Official title: A Multicenter, Multinational, Randomized, Dose-Optimization Study of the Safety and Pharmacodynamic Response of Aldurazyme® (Laronidase) in Patients With Mucopolysaccharidosis I

Study design: Treatment, Randomized, Open Label, Dose Comparison, Parallel Assignment, Safety/Efficacy Study

Primary outcome: To evaluate differences in the pharmacodynamic response and safety of Aldurazyme® (laronidase) does regimens

Minimum age: N/A. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Have a documented diagnosis of MPS I, confirmed by measurable clinical signs and

symptoms of MPS I, and a documented fibroblast or leukocyte α-L-iduronidase enzyme activity level of less than 10% of the lower limit of the normal range of the measuring laboratory.

- Weigh at least 12. 5 kg.

- Have serum creatinine and blood urea nitrogen (BUN) values within age appropriate

normal ranges.

- Provide signed, written informed consent prior to any protocol-related procedures

being performed. Consent of a legally authorized guardian(s) is (are) required for patients under 18 years. If the patient is under 18 years old and can understand the consent, written informed consent will be required from both the patient and the authorized guardian(s).

Exclusion Criteria:

- Have previously received Aldurazyme® (laronidase).

- Have a suspected hypersensitivity to Aldurazyme® (laronidase) or known

hypersensitivity to components of the infusion solution.

- Have previously undergone hematopoietic stem cell transplantation (HSCT; i. e., from

bone marrow [BMT], peripheral blood, or umbilical cord blood) or other major organ transplantation.

- Have a medical condition, serious inter-current illness, or other extenuating

circumstance that may interfere with study compliance including all prescribed evaluations and follow-up activities, except the 6MWT.

Note: All patients may not be capable of performing the 6MWT due to age and/or maturity level. Exemption from performing the 6MWT must be obtained in writing by the investigator from the sponsor's medical monitor prior to enrollment.

- Have an acute illness that requires surgical intervention, and/or anticipates surgery

during study participation, and/or has had surgery within 30 days prior to study enrollment.

- Have received an investigational drug within 30 days prior to study enrollment.

- Is pregnant or lactating. Female patients of childbearing potential must have a

negative pregnancy test [urine β-human chronic gonadotropin (hCG)] at entry (prior to the first infusion). Note: All female patients of childbearing potential and sexually mature males must be advised to use a medically accepted method of contraception throughout the study.

Hospital de Clinical de Porto Alegre, Porto Alegre CEP 90035-003, Brazil

Universidade Federal de Sao Paulo, San Paulo CEP 04023-062, Brazil

Hospital das Clinicas de Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte CEP 30130-100, Brazil

Division of Clinical and Metabolic Genetics, Toronto, Ontario M5G 1X8, Canada

Hospital Infantil Joana de Gusmao, Florianopolis, Santa Catarina CEP 88025-601, Brazil

US FDA Approved Full Prescribing Information for Aldurazyme®

Starting date: April 2004
Ending date: January 2006
Last updated: December 14, 2007